July 14, 2010

March 31, 2010-More than half of donor kidneys in the United State infected with hepatitis C are thrown away, despite the need among hepatitis C patients who may die waiting for an infection-free organ, Johns Hopkins research suggests.

In a study of national data published online in the American Journal of Transplantation, the researchers say that while outcomes are slightly worse when hepatitis C-positive patients receive hepatitis C-positive organs, the advantages of more timely transplants may outweigh the risk of waiting — perhaps more than year — for a hepatitis C-negative kidney.

Patients with hepatitis C-positive make up about 12 percent of the population with kidney failure, and those patients have an increased risk of death on dialysis compared with those without the virus, the study says.

“Nationwide, kidneys from infected donors are inappropriately thrown out and denied to patients in need,” says transplant surgeon Dorry L. Segev, M.D., Ph.D., an associate professor of surgery at the Johns Hopkins University School of Medicine and the study’s leader. “Many transplant centers don’t use these kidneys at all, effectively consigning hepatitis C-positive patients to an average unnecessary wait of a year longer for an uninfected organ.”

That, he says, “means an extra year on dialysis, in which the risk of death is 10 to 15 percent.”

The use of hepatitis C-positive kidneys has been controversial in the past, owing in part to a 1 percent difference in one-year survival for patients who receive the infected kidneys and a 2 percent difference in three-year survival. Segev says this difference “is easily made up for by getting off dialysis sooner.”

Hepatitis C-positive kidneys rarely go to hepatitis C-negative patients because the organ would infect the recipient with the chronic liver disease.

In looking at data from more than 93,000 deceased kidney donors between 1995 and 2009, Segev and his colleagues found that hepatitis C-positive kidneys were two and a half times more likely to be discarded than hepatitis C-negative kidneys. Since 1995, more than 3,500 hepatitis C-positive kidneys were thrown away.

“That’s a lot of kidneys we could have transplanted into people who need them,” Segev says.

Meanwhile, he adds, some 4,800 hepatitis C patients got hepatitis C-negative kidneys. “Using hepatitis C-positive kidneys in people who are infected with the virus could help those with hepatitis C and also expand the organ supply for everyone.”

One-third of the nation’s transplant centers, according to the study, did not use any hepatitis C-positive kidneys for their hepatitis C patients, while 13 percent transplanted more than half of their hepatitis C patients with hepatitis C-positive kidneys.

At The Johns Hopkins Hospital, where doctors specialize in patients with hepatitis C and kidney failure, a patient with hepatitis C could likely be successfully transplanted with a hepatitis C-positive kidney within several months of being put on the waiting list, Segev says. Recipients of hepatitis C-positive kidneys waited, on average, 395 days less than those recipients who waited for hepatitis C-negative kidneys at the same transplant center, the study shows.

Methods
Accurate Dosing in Hepatitis C: Examining the RibaPak Experience (ADHERE) was a U.S., multi-centre, prospective registry capturing data on adherence with RBP vs. RBV in adults with HCV. Adherence was measured by the proportion of subjects remaining on treatment at weeks 4, 12 and 24; by pill counts; and by the proportion of subjects who took ≥80% of their prescribed dose.

Results
A total of 503 patients (RBP = 346, RBV = 157) from 33 sites were included. A greater proportion of RBV vs. RBP subjects prematurely discontinued treatment. At 12 and 24 weeks, a greater proportion of RBP vs. RBV subjects took ≥80% of their prescribed doses (P < 0.05). For patients who remained on treatment, the mean milligrams missed per day was significantly greater for RBV vs. RBP at 24 weeks.

Conclusions
First line treatment with RBP may offer the best prospect for less discontinuation and improved treatment adherence.

WASHINGTON, July 14 /PRNewswire-USNewswire/ -- With millions of Americans living with HIV/AIDS, chronic viral hepatitis, or a combination of both, the National Viral Hepatitis Roundtable (NVHR) welcomes the Administration's recognition of the need for better care coordination and integration of services for these individuals and supports recommendations contained within the new National HIV/AIDS strategy released yesterday in Washington. As the Administration's interagency working group on viral hepatitis works to meet an October 1, 2010 deadline for its own action plan, NVHR is hopeful that we will see a similar national commitment from the Administration. An estimated 5.3 million Americans are infected with chronic viral hepatitis, which is 4 times the estimated HIV/AIDS population. Chronic viral hepatitis is a leading cause of death in HIV patients in America.

"NVHR welcomes the Administration's recognition of the need for better care coordination for individuals afflicted with HIV/AIDS," said Ms. Lorren Sandt, NVHR Chair and Executive Director of Caring Ambassadors Program, based in Portland, OR. "With approximately 30 percent of all individuals living with HIV/AIDS co-infected with hepatitis C and 10 percent co-infected with hepatitis B, an integrated, comprehensive strategy is critical if we are going to win the war against these insidious diseases. The outdated 'silo' approach undermines quality and leads to higher costs throughout the system."

The Administration's national HIV/AIDS strategy provides a model for how to galvanize the entire public health infrastructure into action. With policymakers, clinicians, and other stakeholders seeking to transform our system into one based on preventive care, early intervention to screen, detect, and treat viral hepatitis is essential. With most Americans unaware they are infected, chronic viral hepatitis progresses far too often to liver cancer, cirrhosis, or liver failure. Delayed screening and treatment leads to billions of dollars in avoidable health care costs. Milliman estimates that public and private payers' cost of treating chronic viral hepatitis C alone will more than triple by 2024 to $85 billion unless Washington acts. While proposed legislation would help address this crisis, NVHR believes more needs to be done.

"Just like yesterday's HIV/AIDS announcement, the viral hepatitis plague demands leadership from the highest levels of the federal government," added Ms. Sandt. "Otherwise, millions of Americans will be at risk of developing life-threatening complications."

NVHR is a coalition of more than 150 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. www.nvhr.org

According to a World Health Organization advisor, a number of Malaysians gone overseas for transplantation for their organs were found infected with HIV, hepatitis and a number of other problems.

Prof Dr. Francis Delmonico has been protesting against the criminal practices undertaken while the organs are being supplied, wherein, the tainted organs are approved as such.

He is seeking the introduction of a regulation which can check any such practices worldwide.

“It is time to amend laws and establish a full-time agency to have more and ethical organ donations in the country”, he said.

He also urged the authorities to check for the avoidance in the donations, coming in from cardiac dead patients.

Dr. Delmonico, a WHO adviser on human organ transplantation, said that the organs provided are hardly scrutinized. The organ pools do not provide any guarantee for the quality.

He addressed the co-speakers at a forum on “Organ Trafficking and Transplant Tourism – The Need for Regulatory and Legislative Control” in the 13th Scientific Meeting under the Malaysian Society of Transplantation at the Grand Dorsett Hotel.

Dr. Delmonico said that the marketing of the organs is violating the Istanbul Declaration.

CHICAGO — The five-second rule appears to be alive and well in Illinois same-day surgery centers, where medical staff were observed picking up items that had fallen to the floor and behaving as if they weren't contaminated by germs, according to state inspection reports.

The reports, obtained by The Associated Press through the Freedom of Information Act, detail numerous instances where inspectors saw nurses and other medical staff retrieving dropped materials and then tainting sanitary areas, including in operating rooms. But that wasn't the only problem.

Some of the outpatient clinics -- where procedures include cosmetic surgeries, colonoscopies and laser eye treatments -- cleaned and reused devices that were meant for one person. Doctors were lax about tying their masks before entering surgery. And surgical nurses wore earrings and necklaces banned by clinic policy because jewelry can carry germs into the operating room.

Unsafe clinic practices are a growing concern because of hepatitis C outbreaks in other states linked to reuse of syringes and medication vials. Same-day surgery centers, which can handle some procedures more cheaply than hospitals, are a growing segment of the health care system. No disease outbreaks have been linked to Illinois clinics, but there's no way to tell how many patients, if any, suffered infections because of the problems seen by inspectors.

Of 29 Illinois surgery centers inspected during the past year, 22 -- or nearly 76 percent -- were cited for infection-control problems, a statistic that underscores a problem that has long gone undetected because the state inspected so infrequently.

The number "points to a serious problem that must be addressed to ensure that patients are kept safe from these preventable infections," said Michael McCauley, a spokesman for Consumers Union's Safe Patient Project. The group supports mandatory, public reporting of infection rates at the centers, so patients can easily see a clinic's track record.

The Illinois citations led to repeat inspections in the worst cases, officials said, and all lapses now have been addressed.

But dozens of the state's more than 100 clinics have yet to be inspected with a new sharper-eyed approach.

Previously, inspectors from the Illinois Department of Public Health visited the centers about every seven years. But the state last year began more vigorous and frequent inspections of outpatient surgery centers, following directives from national health officials. The state now plans to inspect a third of Illinois centers each year, said Karen Senger, a supervisor in the Health Department's Division of Health Care Facilities and Programs.

The crackdown resulted from a hepatitis C outbreak in Las Vegas believed to be caused by unsafe injection practices at two now-closed clinics. There have been no similar outbreaks in Illinois.

"This was a result of things that happened in other states," said Bill Bell, acting deputy director for the Office of Health Care Regulation in the Illinois Department of Public Health.

Even so, some of the incidents cited in Illinois inspection reports could have led to problems, Bell said.

For example:

--At a Chicago-area surgery center, a staffer picked up paper that fell to the floor "with her bare hands, and without performing hand antisepsis, she donned gloves and started an intravenous site to (a patient's) left arm," according to the inspector's report.

--In a Springfield operating room, a nurse picked debris off the floor, put the items in the trash and, without washing her hands, returned to duty.

--In a Decatur operating room, a surgical instrument was dropped on the floor, picked up and placed on a clean table, then not removed during cleaning after the surgery ended.

--A package of suture (surgical needle and thread) fell to the floor, was picked up and placed on dressing cart by a staffer at an upscale clinic near Chicago's Michigan Avenue.

--Inspectors discovered that a Chicago surgery center was using a converted commercial dishwasher to sanitize surgical instruments, with no evidence that it was hot enough to kill pathogens.

Patients generally are sedated or unconscious during many of the procedures performed at outpatient surgery centers, so they don't see infection-control lapses going on around them.

"It disturbs me greatly to hear this," said Kim Pongpaet, 37, of Chicago, who had exploratory surgery last year at the 900 North Michigan Surgical Center in Chicago, which was cited for failing to train all staff in infection control and for breaches including the dropped suture package. "I'm disgusted."

The lapses for which the center was cited did not occur during Pongpaet's surgery, and she didn't suffer any infection problems. The center did not respond to AP messages seeking comment.

Mary Goldsher, interim chief executive of DuPage Medical Group, said the state's inspection of DMG Surgical Center in Lombard, which found the center failed to maintain an active infection control program, led to the formation of a committee "whose sole responsibility is carrying out the Infection Control Policy and Program to ensure our patients continue to receive high quality medical care."

The state's effort is meant to raise standards in the centers to more closely mirror what's expected of hospitals, which have had stricter oversight, state officials said.

Earlier this year, U.S. Health and Human Services Secretary Kathleen Sebelius announced her department is expanding its hospital infection control action plan to include ambulatory surgical centers and dialysis centers.

Same-day surgery centers annually perform more than 6 million procedures and collect $3 billion from Medicare.

Previously, Illinois inspectors toured centers and interviewed staff, but rarely spent much time in operating rooms or watched surgeries. Inspectors now follow at least one patient through an entire stay at each clinic. So they're seeing things they wouldn't have seen before, Bell said, including what happens in operating rooms.

Pongpaet was glad to hear state regulators are paying closer attention.

"How does it feel to be patented? There was a sense of betrayal. I mean, they owned a part of me that I could never recover. I certainly have no objection to scientific research ... but it was like a rape. In a sense, you've been violated, for dollars. My genetic essence is held captive."

--John Moore, the subject of US Patent No. 4,438,032

Predictably, Myriad Genetics recently appealed a federal district court's recent decision rendering seven of its lucrative BRCA1 and BRCA2 gene patents invalid. The battle will probably run long, ending only when it reaches the Supreme Court, so the appeal raised hardly a ripple. This stands in contrast to the semantic mayhem triggered by the original ruling

"Pigs fly!" a headline of the Genomics Law Report had wondered, going on to clarify, "Federal Court Invalidates Myriad's Patent Claims." In a ruling the GLR described as "jaw-dropping," "radical," and "astonishing," Judge Sweet of the United States District Court invalidated the patents on the breast- and ovarian-cancer genes, declaring that they are not made by man and thus patent-ineligible.

Genae Girard had been astonished, too, when she learned that women like herself who need genetic testing to quantify their risks and to define the best treatment for their cancer could obtain it only by paying Myriad's $3,400 fee, enabled by the monopoly that the BRCA patents bestow. She resorted to wide-angle legal buckshot, suing not only Myriad and the United States Patent and Trademark Office, and other companies who hold patents on human genes.

Sweet's ruling will resound far beyond the BRCA genes. Biogen Corporation controls your kidney's essential KIM gene; the University of California holds patents on the TCP-1, -2 and -3 genes that enable your tongue to sense taste; and patents have been granted for genes that control the functions human bones, heart, teeth, tongue, colon, skin, brain, bone, ear, lung, liver, kidney, sperm, blood and immune system. 40,000 gene patents have been granted in the US alone.

Spurred by the breadth of the issue, the American Civil Liberties Union rallied to Girard's side, organizing a lawsuit joined by a mammoth coalition of civil libertarians, cancer patients, activists, 100,000 pathologists, and many genetic researchers. All call for an end to gene patents.

The paradigm-shattering agenda of this breathtakingly broad coalition made me question whether its ambitions might be far too.... narrow.

Why? It's true that the USPTO has granted patents on more than 500,000 genes that control the most basic processes of human life. But as I detail in my forthcoming book Deadly Monopolies: The Shocking Corporate Take-Over of Life Itself (Doubleday 2011) what's true of gene patents is doubly true of many other types of life-related patents as well. The $60 billion pharmaceutical industry became the most profitable industry on the planet by exploiting its plethora of patents on not only genes, but also bacteria, viruses, biologicals such as "artificial blood", cell lines, tissues, pharmaceuticals, and even on medically important plants and animals such as Harvard's patented cancer-prone "oncomouse," which are indispensable to medical research. At least 20 human pathogens are privately owned, including haemophilus influenza and Hepatitis C.

This gold rush in life-related patents was promoted to the American public in the 1980s as a means of spurring the development of sorely needed new medications and treatments by fostering closer university-corporation relationships. Tax-supported research at US universities had long been generating medical discoveries when the Supreme Court's 1980 landmark Diamond v Chakrabarty decision came down. Ananda Chakrabarty had tried to patent bacteria that he claimed could address pollution issues by "eating" errant oil spills, but the US Patent Office denied his application on the basis that the bacteria were living entities and only manufactured products were eligible for patents. (This despite the fact that plant patents on hybrids had long been allowed and Louis Pasteur had won a patent for yeast in 1873.) The Chakrabarty ruling permitted patents on a wide variety of living things, including bacteria, viruses, biologicals, and, yes, genes. In the wake of Chakrabarty , many universities took out patents on their tax-supported biomedical discoveries, but, as legislator Birch Bayh lamented, 28,000 patented discoveries developed with $30 billion in taxpayers' dollars were "lying there, collecting dust." Only 5 percent of patented items were being developed into medications, devices or other useful products. According to the US Comptroller General, innovation was being stifled because universities and corporations did not want to invest in developing technology that they did not own. A series of laws rapidly addressed this development vacuum by vigorously catalyzing the transfer of control over medical research from the university to private pharmaceutical and biotechnology corporations such as Myriad. For instance, Bayh partnered with Bob Dole via the "Bayh-Dole Act", that allowed universities to own the resulting tax-supported patents. Subsequent laws, such as the Stevenson-Wydler Technology Innovation Act, encouraged the sale of these patents to industry.

Colleges and universities obtained only about 260 patents a year before 1980's Bayh-Dole Act; today, universities secure 3,000 patents annually, according to the Association of University Technology Managers, and by 1991 they had gleaned $218 million in royalties.

Now, universities receive funds for the patents they assign to private companies and corporate support for the research and development necessary to realize their full value. The corporations receive valuable, ready-made patents on medications, biologicals, genes, devices, plants and animal hybrids that have been underwritten by the federal government and produced by university brainpower. These patents give companies twenty-year monopolies for unfettered profitability as they exploit the patents as they see fit.

And we, the American public, receive promises of a medical bounty in the form of newer, better medications for scourges such as HIV disease, hepatitis C , cancers, drug-resistant tuberculosis, and on a global scale, against killers such as malaria, tuberculosis and sleeping sickness.

The union of the university and industry to spin the dross of neglected patents into the gold of medical innovation is an alchemy that has worked only too well-- but not in the direction we had expected.

Nearly 2800 patents and licenses were granted to North American universities and research institutes by 1991, and hospitals gleaned $218 million in royalties. By 2003, North American university researchers had started 374 companies and academic institutions had completed 4,516 licensing arrangements earning them more than $1.3 billion. By 2006, university technology transfer offices had generated at least $45 billion, largely from licensing fees.

But in place of the promised bounty of new lifesaving medications, we have been left with a dangerous asymmetry in which industry has assumed control of medical research and the university more often resembles a corporation's satellite than an independent entity. The arrangement has eclipsed what Sheldon Krimsky, the author of Science in the Private Interest, called the "public-interest model" of the university, dedicated to public welfare in a wider sense, and one we could depend upon to place national interests above its own and that of its faculty members.

Industry, on the other hand, has focused on maximizing its fiscal return from patents and tends to choose profitability over medical need.

Thus industry controls access to its patents via expensive licensing fees, by discouraging rivals from working on diseases covered by its patents, by developing tests that can be widely administered rather than treatments, and by developing many medications for minor but very common disorders.

For example, Hepatitis C, which affects 170 million people, is the single largest cause of liver transplants in the US . The sole effective medication, interferon b and its variants, is rife with side effects and cures only 1 in 5 who take it. Chiron holds the patent on the HCV virus, but has produced no better treatment. Instead, the price of the hepatitis C virus (HCV) test in the UK increased sixfold in 1994, making it too expensive for England's National Health Service because Chiron had stepped in to aggressively protect its patent. It did so by suing the UK firm Murex for patent infringement and preventing Murex from selling its cheaper HCV blood tests. The suit exerted a chilling effect on researchers who wish to work on better HCV treatments. Roger Williams, director of the Institute of Liver Studies at King's College School of Medicine and Dentistry in London warned ''A situation where one company -- Chiron -- can limit the number of companies carrying out research into hepatitis C must inhibit our knowledge of the disease and our efforts to reduce its spread.''

In 1998, the USPTO granted patents on both mutations of the hereditary hemochromatosis (HFE) gene and SmithKline Beecham Clinical Laboratories obtained an exclusive license that caused other researchers to abandon work on HFE due to the prohibitive costs and the specter of a similar suit.

Multi-drug resistant tuberculosis infects approximately 9 million people every year, including people in affluent Western nations. If none of the four drugs in its treatment regimen works for you, you may die and vaccines are in still "in development." The global scourge of malaria killed 247 million people worldwide in 2006 and some of the eight drugs we deploy against it, such as quinine, have been in use since the 17th century.

By contrast, "erectile dysfunction," coined by Big Pharma to define a quasimedical market for its amorous wares, kills no one, although more than 570 men have died after using one of the more than 14 medications developed since 1996 to treat it. (Big Pharma assures women that "pink Viagra" is en route to them. ) By the measure of drugs developed, erection on demand seems a higher drug-development priority than surviving malaria and tuberculosis.

Trypanosomiasis or "sleeping sickness" epidemics roil Africa regularly, and the fatal ailment infects 66 million people a year. It is treated with Melarsoprol which was discovered in 1949 and is derived from arsenic. It is as toxic as is sounds and kills 1 in 10 people who take it. In 1990 Sanofi-Aventis developed the drug Ornidyl (eflornithine) which is safe and effective against trypanosomiasis but it was withdrawn from the market in 1995 because few poor subSaharan sufferers could afford it. Ornidyl can no longer be bought for love or money but Aventis, and later, Bristol-Myers Squibb, began to market eflornithine to the West as Vaniqa, a prescription-only facial depilatory. Why? Because more Western women can part with $50 a tube to keep their faces hair-free than can subSaharan Africans even save their lives.

Liver cancer is the most common cancer in the world with a life expectancy of three years and few treatment options beyond surgery. Immunologist Chris Parish of Australian National University spent twenty years developing the promising anti-cancer drug known as "PI-88," a double-action drug that slows both the growth and the metastasis of tumors.

In a classic arrangement, Progen Pharmaceuticals Limited, contracted with ANU to pay for the research and development of PI-88 in exchange for ownership of the patent. By late 2008, clinical trials had demonstrated that the drug reduced recurrence rates in liver cancer patients by 35 to 40 per cent and it was ready for Phase III clinical trials, the last stage before approval and availability to the public.

A week before Christmas, however, Progen shut down the trials, voicing concerns about factors "that impacted the commercial return," of PI-88, including the imminent joint launch of Nexavar, a competing drug, by Bayer and Onyx pharmaceutical companies. PI-88 would likely face too much marketplace competition to become the next $1 billion blockbuster, and Progen simply pulled the plug. Because Progen holds the patent on PI-88, Parish cannot go elsewhere to conduct the Phase III trial and pursue its approval.

Industry, which holds the purse strings and the patents, has largely abandoned the quest for cures to pursue cheaper avenues to maximizing profits on virus, medication and tissue patents. Still worse, our very bodies are being mined for corporate profits, with or without our consent. Legal and ethical conflicts with patient interests are inevitable because the tissues in question reside within or emanate from our bodies, but biotech and pharmaceutical companies control them, becoming, in effect, our biological landlords. In 1984, John Moore became the subject of Patent No. 4,438,032 when his physicians David Golde and UCLA surreptitiously patented a cell line from his cancerous spleen. In 1984 Golde struck a $3 billion deal with Sandoz to produce and refine nine valuable cancer-fighting pharmaceuticals produced by Moore's spleen. The organ had been removed as part of Moore's treatment for hairy cell leukemia but Golde had withheld its true value from Moore and misled Moore about the real reason why he was periodically extracting Moore's blood, tissue, bone marrow and semen, not as part of his therapy for the research laboratory. When Moore sued for rights to his own tissues he lost consistently in the courts, culminating in a Supreme Court decision for Golde and UCLA that noted its trepidation that a victory for Moore would have a chilling effect on medical research.

Parents of children with Canavan's disease sued the University of Miami when they discovered that it had also covertly patented the defective ASPA gene isolated from the donated tissues of their doomed children. A plethora of patents have been granted on HeLa cells, taken despite the express refusal of her husband from a Henrietta Lacks a Baltimore housewife who died in 1951.

But today, tissue volume trumps biomedical rarity, which is why anyone who undergoes surgery at hospitals such as Boston's Beth Israel Deaconess is first asked to sign away the ownership rights to his excised tissues to Ardais, a for-profit corporation. "Access to quality human disease tissue is becoming increasingly important to the drug discovery process," declared AstraZeneca vice-president Jeff Hanke, PhD. The resulting medication patents rest on the fruits of our own bodies.

In the same manner in which European colonialists "discovered" continents that were filled with people, US corporations are not above "discovering," patenting and selling the traditional medical remedies, intellectual property and even the gene pools of poor people in the developing world. On March 14, 1995 the US National Institutes of Health (NIH) patented the T-cell line of a Hagahai man from Papua New Guinea.

The Indian government objected after the European Patent Office issued the patent on the medically and culturally important traditional neem tree to the US company W R Grace in 1994 . In 2005 the Havasupai tribe sued Arizona State University researchers for stigmatizing schizophrenia research the ASU conducted without consent on 400 blood samples from the tribe's members. In mid 1990s asthma-prone residents of the isolated Tristan da Cunha a island in the South Atlantic lost the battle for control of their own genetic material after it was collected and patented and provided to Sequana Therapeutics Incorporated and Boehringer Ingelheim by Canadian researchers who hoped to locate a gene that predisposing people to asthma. Estimated its cost at $70 million. The gene pools of not only Tristan de Cunha but even Western nations such as Iceland have been patented for profit under questionable models of consent.

Why is the industry permitted to pursue profits unchecked by considerations of health or affordability? Because desultory FDA oversight and revolving-door lobbyists have midwifed loose regulation that allows pharmaceutical and biotech companies to set their own prices without government restraint. Fully half of health-care lobbyists are former government officials, cutting deals with their erstwhile colleagues for the industry's benefits and special protections.

The pharmaceutical industry, for example was the largest beneficiary of healthcare reform legislation. Companies such as Johnson & Johnson, Pfizer, and Merck enjoy profits that averaged between $2 to 10 billion in 2008, making Pharma the nation's third most profitable industry, while the health insurance industry ranks a distant 28th. Yet the latter is heavily controlled by reform while the former emerges unscathed, for the 2010 Patient Protection and Affordable Care Act failed to tighten federal regulation of medical products, to regulate pharmaceutical drugs, and utterly avoided price controls.

Some argue that gene patents are necessary to generate the profits essential to funding the medical cures. But as the cases of breast cancer, hepatitis C and hemochromatosis illustrate, genes are more commonly used for faster, easier routes to profit, such as marketing tests, selling licenses and suing those patent-infringers who step on the corporation's biomedical toes. As Sheldon Krimsky has observed, "The public ethos of science slowly disappears, to the detriment of the communitarian interests of society."

About 130 million people are infected with the hepatitis C virus (HCV) worldwide, but effective treatment options are not yet available. One of the most promising targets for antiviral therapy is nonstructural protein 3 (NS3).

To identify possible changes in the structure of NS3 associated with virological sustained response or non-response of patients, a model was constructed for each helicase NS3 protein coding sequence. From this, the goal was to verify the interaction between helicases variants and their ligands.FindingsEvidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites.

K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor.

Conclusions: Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site.

Previously, we have reported the isolation and molecular characterization of human Hepatitis C virus genotype 1 (HCV-1) from infected patients. We are now reporting an analysis of HCV obtained from patients infected with HCV genotype 3 (HCV-3) as diagnosed by clinical laboratories.

Results

HCV was cultured in vitro using our system. HCV RNA was isolated from patients' blood and from HCV cultured in various cell types for up to three months. The 5'UTR of these isolates were used for comparisons. Results revealed a number of sequence changes as compared to the serum RNA. The HCV RNA produced efficiently by infected macrophages, B-cells, and T-cells had sequences similar to HCV-1, which suggests that selection of the variants was performed at the level of macrophages. Virus with sequences similar to HCV-1 replicated better in macrophages than HCV having a 5'UTR similar to HCV-3.

Conclusions

Although HCV-3 replicates in cell types such as B-cells, T-cells, and macrophages, it may require a different primary cell type for the same purpose. Therefore, in our opinion, HCV-3 does not replicate efficiently in macrophages, and patients infected with HCV-3 may contain a population of HCV-1 in their blood.

The complete article is available as a provisional PDF.
The fully formatted PDF and HTML versions are in production.

There is a silent crisis affecting America. This crisis endangers 5.3 million people in the U.S. and is more common than HIV/AIDS, yet it remains unrecognized as a serious public health threat. The crisis: viral hepatitis. Most people who have it are unaware, that is until they develop cancer or liver disease years later. Given this national tragedy in the making, we must educate people on the pervasiveness of Hepatitis B and Hepatitis C, identify effective measures on viral hepatitis prevention, control and surveillance programs, and provide a mechanism to implement these measures.

It is not a misnomer to call this a silent crisis. Few people realize how highly infectious viral hepatitis is. Hepatitis B is 100 times more infectious than HIV. Few realize that, left untreated, it can cause liver disease, liver cancer and premature death decades after infection. Few realize that about 2 billion people worldwide have been infected with Hepatitis B; more than 170 million people are chronically infected with Hepatitis C. Tragically, two-thirds of those infected, on average, are unaware of their status, which increases the chance of spreading the disease.

We cannot afford to be silent anymore. Our countrymen and women are dying daily, needlessly, from a disease that is entirely preventable if detected early. Each year, about 15,000 people die from liver cancer or liver diseases related to Hepatitis B and Hepatitis C. That’s more than 40 Americans dying every day, with no state or district in our nation exempt from its deadly reach.

Beyond the tragic and preventable loss of human life, the costs to our country are explicitly economic as well. Without effective prevention and vaccination methods in place, chronic Hepatitis B and C are expected to cost our country at least $20 billion in treatments during the next 10 years. As a result, over the same time frame, commercial and Medicare costs will more than double. Projecting further out, over the next 20 years, total medical costs for patients with Hepatitis C infection are expected to increase more than 2.5 times from $30 billion to more than $85 billion.

Contrast the costs for early detection and intervention with the costs for treatment post-infection. Hepatitis B vaccinations are $60, whereas treatment can cost up to $16,000 per year. Screening for Hepatitis C is $8 compared to treatment that can cost up to $25,000 per year. Untreated, these infections will develop into liver disease that can cost up to $110,000 per hospital admission.

We must, therefore, change the way hepatitis is diagnosed and treated. The Institute of Medicine (IOM) report on “Hepatitis and Liver Cancer” corroborates this conclusion by calling for a national strategy in the prevention and control of Hepatitis B and C. The report concludes that the current approach to the prevention and control of chronic Hepatitis B and C is not working. As a remedy, the IOM recommends increased knowledge and awareness about chronic viral hepatitis among health care providers, social service providers, and the public; improved surveillance for Hepatitis B and Hepatitis C; and better integration of viral hepatitis services.

My call for a national strategy is not unlike IOM’s. With bipartisan support, I introduced the Viral Hepatitis and Liver Cancer Control and Prevention Act, H.R. 3974, which provides almost $600 million over the next five years to treat hepatitis. The legislation mirrors many of the IOM’s recommendations and focuses federal efforts on a strategy that saves lives and makes our health system more efficient.

Specifically, H.R. 3974 increases interagency coordination between the Centers for Disease Control, National Institute for Health, National Cancer Institute, the Health Resource and Service Administration Agency for Healthcare Research and Quality and Veteran Affairs. It does so by implementing programs to increase awareness and enhance knowledge and understanding of Hepatitis B and C and requiring the CDC to integrate into existing programs immunization, prevention, and control programs and support counseling. The legislation expands current vaccination programs and establishes a national chronic and acute Hepatitis B and C surveillance program to identify incidence and prevalence in viral hepatitis and liver cancer.

Pass this bill and we bring together the common concerns of the diverse viral hepatitis community to fight chronic viral hepatitis by establishing, promoting and supporting a comprehensive prevention, research and medical management referral program. And we strengthen the ability of the CDC to support state health departments in the prevention, immunization and surveillance efforts.

Through this legislation, and with strategic investments in public health and prevention programs, billions of dollars can be saved, and so, too, the lives of tens of thousands of people in states and cities all over America. I urge all of you to join me in supporting activities that promote early detection and education. With your help, we can sound the alarm on this silent crisis.

Rep. Honda is the Chairman of the Congressional Asian Pacific American Caucus.

SAN FRANCISCO--(BUSINESS WIRE)--Presidio Pharmaceuticals, Inc. announced today the successful completion of a Phase 1a clinical trial of PPI-461, its lead HCV NS5A inhibitor, in healthy subjects. This first-in-human trial evaluated four single doses of PPI-461, followed by a five-day, once-a-day treatment regimen with PPI-461 at the highest tested dose.

The randomized, double-blind, placebo-controlled trial was completed with 40 healthy subjects in the United Kingdom. The trial results indicated that PPI-461 was well-tolerated in all dose regimens. There were no serious adverse events, and all subjects completed the trial successfully. Among PPI-461 recipients there were only transient adverse events, none of which were attributed to study drug by the investigator, and there were no significant changes in safety-related clinical laboratory assessments.

Pharmacokinetic (PK) analyses showed substantial blood levels of PPI-461 were rapidly and consistently achieved and were dose proportional. PPI-461 plasma concentrations were orders of magnitude above those shown to suppress viral replication in vitro and were maintained at predicted effective concentrations for more than 24 hours. In the five-day, multi-dose regimen, steady-state PK was readily achieved, supportive of once-daily dosing.

“These first clinical data of PPI-461 indicate excellent tolerance in healthy subjects with all tested dosing regimens. The PK profile is very encouraging, suggesting that plasma concentrations of PPI-461 can be obtained with a relatively low dose, once-daily (QD) regimen that may provide a continuous antiviral effect,” said Nathaniel Brown, M.D., Chief Medical Officer.

Presidio Pharmaceuticals, Inc. plans to initiate a Phase 1b proof-of-concept trial in patients with HCV in Q4 2010 and expects to have early results regarding the clinical efficacy of PPI-461 near year-end.

Inhibitors of the HCV NS5A protein represent an exciting, highly potent class that is distinct from other classes of HCV antivirals that target the viral protease or replicase. With poor response and tolerance issues associated with the current standard of care treatment—pegylated-IFN and ribavirin—there is clear need for more potent and better tolerated inhibitors that can be orally administered in future combination therapies.

ABOUT PRESIDIO

Presidio Pharmaceuticals, Inc. is a San Francisco-based specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics for novel and validated targets. For more information, please visit our website at: http://www.presidiopharma.com/.

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